Collectively, anti-HER2 IgE maintains Fab-mediated antitumor activity, induces Fc-mediated effects against HER2-expressing tumor cells, and stimulates remodeling of the immune microenvironment in tumors to promote pro-inflammatory cell phenotypes which could translate to improved outcomes for patients.

Before neoadjuvant chemotherapy combined with H and P dual-target therapy, ALT levels were associated with pCR. After the treatment, GGT levels were linked to pCR. This treatment regimen was associated with increased blood levels of ALT, AST, LDH, and GGT.

P1, N=149, Not yet recruiting, Qilu Pharmaceutical Co., Ltd.

P2, N=39, Active, not recruiting, The Methodist Hospital Research Institute | Recruiting --> Active, not recruiting | Trial completion date: Feb 2025 --> Dec 2025

Such dynamic fluctuation of receptor interaction may open a window for the binding of therapeutic antibodies that are aimed at inhibiting heterodimerization, such as pertuzumab. The complementary array of state-of-the-art imaging cytometry approaches thus demonstrates a spatiotemporal pattern of spontaneous and induced receptor aggregation states that could provide mechanistic insights into the potential success of targeted therapies directed at the HER family of receptor tyrosine kinases.

The HER2/PET-CT biomarker had high prediction power for pCR, however was not superior to the prediction power of PET/CT alone. Non-invasive PET/CT biomarkers may facilitate a response-guided approach to neoadjuvant therapy, allowing intensification and de-intensification of treatment, pending further evaluation.

These data provide a robust preclinical characterization of XMT-2056 and provide rationale and strategy for its clinical testing.

P3, N=922, Recruiting, Hoffmann-La Roche | Trial primary completion date: Mar 2027 --> Dec 2027

P2, N=63, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> May 2025

P2, N=171, Completed, European Organisation for Research and Treatment of Cancer - EORTC | Active, not recruiting --> Completed | Trial completion date: Dec 2028 --> Dec 2024

P2, N=23, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Nov 2024 --> Nov 2025

P2, N=220, Completed, West German Study Group | Active, not recruiting --> Completed

Additionally, we identified key proteins, including ANXA1, SLC2A1, and PPIG, which contribute to the tumour progression and resistance phenotype. Our study suggests that targeting these pathways and proteins could form the basis of novel therapeutic strategies to overcome resistance in HER2-positive breast cancer.

Pyrotinib combined with trastuzumab may offer an effective neoadjuvant treatment option for HER2-positive breast cancer, with a superior efficacy over trastuzumab alone. However, pyrotinib plus trastuzumab did not show better efficacy compared with Per + H. Pyrotinib plus trastuzumab was associated with more diarrhrea than trastuzumab monotherapy. In addition, P + H is less cost-effective compared with the combination of Per + H.

P2, N=170, Recruiting, UNICANCER | Not yet recruiting --> Recruiting

P=N/A, N=80, Completed, Fondazione Oncotech

P3, N=347, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Mar 2025 --> Nov 2024

P3, N=230, Recruiting, Hoffmann-La Roche | Trial completion date: Jan 2028 --> Dec 2032

Pertuzumab and pyrrolizinib target HER-2 to downregulate the PI3K/AKT signaling pathway, thereby inhibiting breast cancer cells.

Chemotherapy was initiated with a regimen of paclitaxel, trastuzumab, and pertuzumab...However, after 9 months of treatment, disease progression occurred, leading to sequential changes in the treatment regimen to T-DM1 and T-DXd...Postoperatively, the patient received radiation therapy to the chest wall, followed by continued treatment with trastuzumab and pertuzumab. As of 2 years after surgery, no recurrence has been observed.

Without distant metastasis, the patient received doxorubicin plus cyclophosphamide( AC)therapy followed by trastuzumab, pertuzumab, docetaxel(HPD)therapy as neoadjuvant chemotherapy. Subseqently, the tumor disappeared clinically. Mastectomy was performed, and complete response was confirmed pathologically.

P2, N=2, Active, not recruiting, Spanish Breast Cancer Research Group | Recruiting --> Active, not recruiting | N=41 --> 2

P2, N=63, Recruiting, Latin American Cooperative Oncology Group | Not yet recruiting --> Recruiting

P2, N=74, Not yet recruiting, University of Chicago | Initiation date: Jan 2025 --> Jan 2026

The standard of care for HER2-positive and hormone receptor-positive breast cancer patients who receive neoadjuvant chemotherapy (NACT) combined with trastuzumab, with or without pertuzumab, is to continue with adjuvant T-DM1 in cases of an incomplete response according to KATHERINE trial results. However, the optimal management for patients with residual disease with loss of HER2 expression is not widely studied. Loss of HER2 expression after NACT with anti HER2 is a rarer event with questionable value both as a predictive prognostic marker.

Subsequently, she underwent post-operative chemotherapy regimen of doxorubicin, cyclophosphamide, T-docetaxel and trastuzumab (AC-TH) and then received maintenance treatment with trastuzumab and pertuzumab. If possible, dual anti-HER2 therapy combined with trastuzumab and pertuzumab is recommended. Finally, positive clinical prognosis of PBSCC may be attributed to early detection, immediate surgery, precise diagnosis and proper adjuvant treatment strategy.

Median PFS by independent review did not show the difference between the two groups (4.4 v 4.4 months; HR, 1.03 [one side 95% CI upper limit, 1.36]). These findings suggest that dual HER2 blockade with pertuzumab plus trastuzumab could contribute to improving OS in patients who have previously been treated with pertuzumab-containing regimens for HER2-positive LA/mBC.

P2, N=18, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Jun 2025

The HER2DX pCR score could predict pCR in stage III HER2-positive IBC following treatment with de-escalated neoadjuvant systemic therapy and in stage III HER2-positive non-IBC. Elevated pCR rates in HER2-positive IBC with high HER2DX pCR scores suggest there may be a role for treatment de-escalation in these patients and confirmatory studies are justified.

P=N/A, N=300, Cancer Hospital Affiliated to Shandong First Medical University; Cancer Hospital Affiliated to Shandong First Medical University

P=N/A, N=120, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine; Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

P2, N=78, Sichuan Cancer Hospital; Sichuan Cancer Hospital

P1, N=100, Completed, Beijing shijitan hospital affiliated to capital medical university; Beijing shijitan hospital affiliated to capital medical university

AI-powered HER2 QCS and TME analysis demonstrated potential in enhancing treatment response predictions in patients with HER2-amplified mCRC undergoing TP therapy.

P2, N=240, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Nov 2024 --> Nov 2025

P3, N=4804, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed

Additionally, Ptz-SA also exhibits binding capacity to HER2 (S310Y), another mutation occurring at the S310 site of HER2 with high frequency. The computational-aided evolution of pertuzumab provides an alternative strategy for overcoming point mutation-mediated resistance to therapeutic antibodies.

P2, N=16, Active, not recruiting, Fox Chase Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Dec 2025

P2, N=20, Active, not recruiting, Mayo Clinic | Trial completion date: Dec 2024 --> Aug 2025

P3, N=154, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Dec 2025 --> May 2026 | Trial primary completion date: Dec 2025 --> May 2026

P1, N=60, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

Interestingly, these affitins do not compete with the commonly used monoclonal antibodies trastuzumab and pertuzumab for HER2 binding sites, allowing their concurrent use in vivo and making them suitable for imaging or diagnostic purposes. These findings indicate that targeted competitive binding assays could efficiently reduce the experimental efforts to map the HER2-affitin interactions. The computational approach proposed in this study not only provides insights into this specific case but also establishes a robust framework applicable for facilitating the structural modeling and interaction prediction of other affitin-protein systems.